Genome-wide analysis of in vivo TRF1 binding to chromatin restricts its location exclusively to telomeric repeats.

Abstract

Telomeres are nucleoprotein structures at the ends of eukaryotic chromosomes that protect them from degradation, end-to-end fusions, and fragility. In mammals, telomeres are composed of TTAGGG tandem repeats bound by a protein complex called shelterin, which has fundamental roles in the regulation of telomere protection and length. The telomeric repeat binding factor 1 (TERF1 or TRF1) is one of the components of shelterin and has been shown to be essential for telomere protection. Telomeric repeats can also be found throughout the genome, as Internal or Interstitial Telomeric Sequences (ITSs). Some of the components of shelterin have been described to bind to ITSs as well as other extra-telomeric regions, which in the case of RAP1 exert a key role in transcriptional regulation. Here, we set to address whether TRF1 can be found at extra-telomeric sites both under normal conditions and upon induction of telomere shortening. In particular, we performed a ChIP-sequencing technique to map TRF1 binding sites in MEFs wild-type and deficient for the telomerase RNA component (Terc(-/-)), with increasingly short telomeres. Our findings indicate that TRF1 is exclusively located at telomeres both under normal conditions, as well as under extreme telomere shortening. These results indicate that in mice not all members of shelterin have extra-telomeric roles as it was described for RAP1.